Quality by design approach for simultaneous determination of original active pharmaceutical ingredient quinabut and its impurities by using HPLC. Message 1

Aim. The aim of study was to develop and validate a simple, highly robust (quality by design (QbD) approach), precise and accurate method using high performance liquid chromatography for the simultaneous determination of original active pharmaceutical ingredient Quinabut and its impurities. Materials and methods. Experiments were performed on a Shimadzu LC-20 Prominence HPLC separation module, equipped with a quaternary gradient pump, temperature controlled column heater, sampler manager and diode array detector and LC-20 Chemstation for data analysis (Shimadzu Corporation, Japan). Same software was used for data acquisition and processing of results. X-Terra RP18 (4.6×150 mm, 5 μm) analytical chromatographic column provided by Waters Corporation (Milford, MA) was used for all optimization experiments. Mobile phase A: acetonitrile R. Mobile phase B: 0.025 M phosphate buffer solution. Samples were chromatographed in gradient mode. Flow rate of the mobile phase: 0.7 mL/min. Column temperature: 40 °С. Detection: at 233 nm wavelength. Injection volume: 50 μl. Results. Screening of the influence of four chromatographic factors on different chromatographic responses was performed as the initial step of analytical method optimization. A randomized fractional factorial experimental design (24–1) of resolution IV with central point was used. Buffer pH, amount of acetonitrile in mobile phase A, the amount of phosphate buffer solution in mobile phase B and column temperature were selected as factors of interest, and were used to generate the fractional factorial experimental design. Linearity was established in the range of LOQ level to 0.2% having regression coefficients 0.9977. Calibration curve – y = 0.0132 + 0.9902. Since Δt for the content of quinabut is less than max δ, the technique is stable over time. The possibility of contamination of the sample by decomposition products by keeping it under stressful conditions (irradiation of the substance solution with UV light (UV irradiation with mercury lamp light); acid hydrolysis with 0.1 M hydrochloric acid solution; oxidative decomposition) was investigated. As a result of the irradiation with UV light, the impurity peaks for about 8.74 min (impurity C) and 12.68 min (impurity B) are additionally revealed. Their content exceeds the limits of normalization and is 0.6% and 3.7%, respectively. Therefore, the powder of the substance and its solutions should be stored away from direct sunlight. The column temperature and the speed of the mobile phase within ± 10% did not significantly affect the test results. The results were found to be within the assay variability limits during the entire process. Conclusion. 1) The optimization of a new analytical method capable of simultaneous determination of quinabut assay and its impurities drug products was performed with a single fractional factorial experimental design. Only 11 experiments were needed for the optimization, while at least 16 experiments would be needed to cover the same analytical method operational region of the first optimization step with a traditional one factor at time (OFAT) approach. 2) HPLC method was developed and validated for the simultaneous detection and quantitation of quinabut and its impurities. 3) The final analytical method optimized with QbD approach was validated according to ICHQ2R1 guideline. The method proved to be sensitive, selective, precise, linear, accurate and stability-indicating. 4) The method was successfully applied to the analysis of demonstrating acceptable precision and adequate sensitivity for the detection and quantitation of quinabut and its impurities. So it may be reasonable to claim that the method can be extended to the analysis of drug formulations and stability samples as well. This optimization reflects in saving of time and resources since one stability study includes hundreds of samples tested during the product’s shelf life.

Utilization of Quarry Dust and Calcareous Fly Ash for the Production of Lightweight Cellular Micro-Concrete—Synthesis and Characterization

This study aims to assess the production of cellular micro-concrete, consisting of quarry dust, calcareous fly ash, cement, and aluminum powder as aerating agent. The proposed mixture design methodology is based on a Box–Behnken fractional factorial experimental design. Testing of specimens included compressive and flexural strength, density, water absorption, and thermal conductivity measurements. Results indicate that density is a characteristic property which determines all the measured properties. Aerating agent to cement and fly ash ratio has the strongest effect on all the measured properties. The developed methodology is a valuable tool for the production of cellular micro-concrete with predetermined properties by utilizing large amounts of quarry dust.

The β-cyclodextrin-modified nanosized ZSM-5 zeolite as a carrier for curcumin

Herein, the nanosized ZSM-5 zeolite was synthesized based on a fractional factorial experimental design by a hydrothermal method to study the optimum conditions for the synthesis and formation of the ZSM-5 zeolite by employing different conditions.

Magnetron Sputtered AlN Layers on LTCC Multilayer and Silicon Substrates

This work compares the deposition of aluminum nitride by magnetron sputtering on silicon to multilayer ceramic substrates. The variation of sputter parameters in a wide range following a fractional factorial experimental design generates diverse crystallographic properties of the layers. Crystal growth, composition, and stress are distinguished because of substrate morphology and thermal conditions. The best c-axis orientation of aluminum nitride emerges on ceramic substrates at a heater temperature of 150 °C and sputter power of 400 W. Layers deposited on ceramic show stronger c-axis texture than those deposited on silicon due to higher surface temperature. The nucleation differs significantly dependent on the substrate. It is demonstrated that a ceramic substrate material with an adapted coefficient of thermal expansion to aluminum nitride allows reducing the layer stress considerably, independent on process temperature. Layers sputtered on silicon partly peeled off, while they adhere well on ceramic without crack formation. Direct deposition on ceramic enables thus the development of optimized layers, avoiding restrictions by stress compensating needs affecting functional properties.

Performance das variáveis operacionais na transesterificação etílica do óleo de soja

The following operational variables in the ethylic transesterification of soybean oil were evaluated using the fractional factorial experimental design: (1) time (2) stirring speed, (3) molar ratio ethanol: triglycerides, (4) ratio of catalyst for the mass of oil (5) type of catalyst and (6) temperature. The levels for each variable studied were: (1) time, 30 and 60 minutes, (2) speed, 100 and 200 rpm, (3) molar ratio ethanol: triglycerides, 9:1 and 12:1, (4) proportion of catalyst in relation to the mass of oil, 0.5% and 1.5% (5) type of catalyst, sodium hydroxide or potassium and (6) temperature, 35 ° C and 55 ° C. The order of magnitude of the effect observed for each of these factors in terms of income, the transesterification was: concentration of the catalyst> catalyst type> molar ratio > time> temperature> speed. In this work we studied the interactions between the variables and their implications in the transesterification process via ethylic route for soybean oil. The interactions between the variables (1) and (6), (1) and (2), (1) and (5), (2) and (4) were significant and positive for the process, ie it, followed the trends the individual effects of the main variables of the interaction will be favored income. Interactions: (2) and (6), (1) and (3), (1) and (4) proved to be negative and significant which implies that followed the trends of the individual effects of the interaction of the main variables, yields biodiesel production will decrease.

Improvement of Quality of Gluten-free Layer Cakes

The development and study of new gluten-free foods of high quality that are suitable for people with celiac disease is necessary since there is increasing frequency of people who have been found to be allergic to proteins in wheat flour. Rice is one of the most used cereals in these special foods elaborations. However, replacement of wheat flour by rice flour usually leads to a noticeable decrease in the quality of the products discussed in this study. This work studied the individual and combined influence of xanthan gum (XAN), emulsifier, pregelatinizated starch, and transglutaminase on quality of rice yellow layer cake (YLC) by means of a systematic study based on a two-level half-fractional factorial experimental design. Size and shape, texture, color, crumb grain profile and sensory acceptance were evaluated in YLC. XAN, white egg proteins, and emulsifier showed significant positive effects on volume, texture and crumb grain characteristics. The feasibility of rice YLC reaching acceptable levels of customer satisfaction was demonstrated.